1,3-Dichloroacetone → 3-(4-chloromethyl-thiazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 1737371Notes

Reaction equation

HRID 1737371 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:15](=[S:17])[NH2:16])=[C:10]3[CH2:9][N:8]([CH3:18])[C:7](=[O:19])[C:6]=2[CH:20]=1.[Cl:21][CH2:22][C:23](=O)[CH2:24]Cl>O1CCOCC1>[Cl:21][CH2:22][C:23]1[N:16]=[C:15]([C:14]2[N:13]=[CH:12][N:11]3[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:20][C:6]=4[C:7](=[O:19])[N:8]([CH3:18])[CH2:9][C:10]=23)[S:17][CH:24]=1

Participants

4

Reactant 2

HCID 107931,3-DichloroacetoneHCID 21842253HCID 21842253, compound

Product 1

HCID 218422963-(4-chloromethyl-thiazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-oneYield 57.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A suspension of 4.51 g (0.0155 mol) of 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-thiocarboxamide in 100 ml of dioxan was treated with 2.16 g (0.0171 mol) of 1,3-dichloro-2-propanone. The suspension was boiled at reflux for 41 hrs., cooled and completely freed from the solvents. The residue was chromatographed over silica gel with dichloromethane/ethyl acetate 1:1 as the eluent and recrystallized from hot ethyl acetate. There were obtained 3.23 g (57%) of 3-(4-chloromethyl-thiazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one as white crystals; m.p. 239-241°.

Workup

  1. temperatureat reflux for 41 hrs
  2. temperature, cooled
  3. customThe residue was chromatographed over silica gel with dichloromethane/ethyl acetate 1:1 as the eluent
  4. customrecrystallized from hot ethyl acetate

Sources & evidence

ORD record
ord-0e184ab586304f2f8654fbf20aa28b3f
Source dataset
uspto-grants-1999_10
Patent number
US05962450

Reaction notes

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